Synaptic resilience is associated with maintained cognition during ageing

Declan King; Kris Holt; Jamie Toombs; Xin He; Owen Dando; Judith A. Okely; Makis Tzioras; Jamie Rose; Ciaran Gunn; Adele Correia; Carmen Montero; Hannah McAlister; Jane Tulloch; Douglas Lamont; Adele M. Taylor; Sarah E. Harris; Paul Redmond; Simon R. Cox; Christopher M. Henstridge; Ian J. Deary; Colin Smith; Tara L. Spires-Jones

doi:10.1002/alz.12894

Synaptic resilience is associated with maintained cognition during ageing

Declan King, Kris Holt, Jamie Toombs, Xin He, Owen Dando, Judith A. Okely, Makis Tzioras, Jamie Rose, Ciaran Gunn, Adele Correia, Carmen Montero, Hannah McAlister, Jane Tulloch, Douglas Lamont, Adele M. Taylor, Sarah E. Harris, Paul Redmond, Simon R. Cox, Christopher M. Henstridge, Ian J. DearyColin Smith, Tara L. Spires-Jones (Lead / Corresponding author)

Centre for Advanced Scientific Technologies

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

106 Downloads (Pure)

Abstract

Introduction: It remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing.

Methods: We examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate.

Results: Synaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline.

Discussion: Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.

Original language	English
Pages (from-to)	2560-2574
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	19
Issue number	6
Early online date	22 Dec 2022
DOIs	https://doi.org/10.1002/alz.12894
Publication status	Published - Jun 2023

Keywords

Alzheimer's
ageing
cognition
synapse

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/alz.12894Licence: CC BY-NC

Final Published VersionFinal published version, 2.84 MBLicence: CC BY-NC

Cite this

King, D., Holt, K., Toombs, J., He, X., Dando, O., Okely, J. A., Tzioras, M., Rose, J., Gunn, C., Correia, A., Montero, C., McAlister, H., Tulloch, J., Lamont, D., Taylor, A. M., Harris, S. E., Redmond, P., Cox, S. R., Henstridge, C. M., ... Spires-Jones, T. L. (2023). Synaptic resilience is associated with maintained cognition during ageing. Alzheimer's and Dementia, 19(6), 2560-2574. https://doi.org/10.1002/alz.12894

@article{0f4b6798c4b649fd924df09889fe5896,

title = "Synaptic resilience is associated with maintained cognition during ageing",

abstract = "Introduction: It remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing.Methods: We examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate.Results: Synaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline.Discussion: Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.",

keywords = "Alzheimer's, ageing, cognition, synapse",

author = "Declan King and Kris Holt and Jamie Toombs and Xin He and Owen Dando and Okely, {Judith A.} and Makis Tzioras and Jamie Rose and Ciaran Gunn and Adele Correia and Carmen Montero and Hannah McAlister and Jane Tulloch and Douglas Lamont and Taylor, {Adele M.} and Harris, {Sarah E.} and Paul Redmond and Cox, {Simon R.} and Henstridge, {Christopher M.} and Deary, {Ian J.} and Colin Smith and Spires-Jones, {Tara L.}",

note = "Funding Information: Biotechnology and Biological Sciences Research Council Grant Number: BB/W008793/1; Medical Research Council. Grant Number: MR/M01311/1; Wellome Trust. Grant Number: 628TRN R46470 the Wellcome Trust and the Royal Society. Grant Number: 221890/Z/20/Z; Economic and Social Research Council new investigator. Grant Number: ES/S015604/1; the European Union's Horizon 2020 research and innovation programme. Grant Number: 681181; UK Dementia Research Institute. Grant Number: DRI-Edin005 Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = jun,

doi = "10.1002/alz.12894",

language = "English",

volume = "19",

pages = "2560--2574",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Wiley",

number = "6",

}

King, D, Holt, K, Toombs, J, He, X, Dando, O, Okely, JA, Tzioras, M, Rose, J, Gunn, C, Correia, A, Montero, C, McAlister, H, Tulloch, J, Lamont, D, Taylor, AM, Harris, SE, Redmond, P, Cox, SR, Henstridge, CM, Deary, IJ, Smith, C & Spires-Jones, TL 2023, 'Synaptic resilience is associated with maintained cognition during ageing', Alzheimer's and Dementia, vol. 19, no. 6, pp. 2560-2574. https://doi.org/10.1002/alz.12894

TY - JOUR

T1 - Synaptic resilience is associated with maintained cognition during ageing

AU - King, Declan

AU - Holt, Kris

AU - Toombs, Jamie

AU - He, Xin

AU - Dando, Owen

AU - Okely, Judith A.

AU - Tzioras, Makis

AU - Rose, Jamie

AU - Gunn, Ciaran

AU - Correia, Adele

AU - Montero, Carmen

AU - McAlister, Hannah

AU - Tulloch, Jane

AU - Lamont, Douglas

AU - Taylor, Adele M.

AU - Harris, Sarah E.

AU - Redmond, Paul

AU - Cox, Simon R.

AU - Henstridge, Christopher M.

AU - Deary, Ian J.

AU - Smith, Colin

AU - Spires-Jones, Tara L.

N1 - Funding Information: Biotechnology and Biological Sciences Research Council Grant Number: BB/W008793/1; Medical Research Council. Grant Number: MR/M01311/1; Wellome Trust. Grant Number: 628TRN R46470 the Wellcome Trust and the Royal Society. Grant Number: 221890/Z/20/Z; Economic and Social Research Council new investigator. Grant Number: ES/S015604/1; the European Union's Horizon 2020 research and innovation programme. Grant Number: 681181; UK Dementia Research Institute. Grant Number: DRI-Edin005 Copyright: © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2023/6

Y1 - 2023/6

N2 - Introduction: It remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing.Methods: We examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate.Results: Synaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline.Discussion: Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.

AB - Introduction: It remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing.Methods: We examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate.Results: Synaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline.Discussion: Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.

KW - Alzheimer's

KW - ageing

KW - cognition

KW - synapse

UR - http://www.scopus.com/inward/record.url?scp=85145070538&partnerID=8YFLogxK

U2 - 10.1002/alz.12894

DO - 10.1002/alz.12894

M3 - Article

C2 - 36547260

SN - 1552-5260

VL - 19

SP - 2560

EP - 2574

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Synaptic resilience is associated with maintained cognition during ageing

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this